The proposed research is a continuation of our investigations of murine myeloma cells in vitro and in vivo. It is planned to study further the phenomenon of loss of oncogenicity which has been observed to occur spontaneously within a relatively short period after these cells have been established in continuous suspension culture. Characteristics of the myeloma cells which correlate with this loss of oncogenicity will be evaluated, such as in vitro proliferation, ultrastructure, globulin synthesis, viral content, chromosomal content as well as physico-chemical and immunological characteristics of the cell membrane. Attempts will be made to control or modulate the particular differentiated function of these cells, namely globulin synthesis by altering cell concentration, medium pH, serum concentration, temperature, and it is planned to relate this differentiated function to other cell characteristics. Attempts will be made to modulate the tumor growth in vivo by seeking means of inhibiting the oncogenicity or lethality of transplanted tumor cells by modification of the host immunological responses. Furthermore, it is desired to study the effects of superimposed viral infections on the various characteristics of the myeloma cells and also to followup recently described new leads which may allow further determination of the etiologic significance of the viral particles which are found in murine myeloma cells. Beyond these studies, it is planned to continue attempts to establish human myeloma cells in continuous culture in vitro, apply the same approaches as used for the murine cells to the human cells to the extent that this is possible and/or feasible, and in particular, attempt to utilize initially established human myeloma cell cultures to evaluate the usefulness of particular chemotherapeutic approaches.